Regulatory Decision Summary for Zolgensma

Spinal muscular atrophy (SMA) is a rare neuromuscular disorder caused by deletion or mutation of the survival motor neuron 1 (SMN1) gene resulting in the deficiency of functional SMN protein, which is essential for motor neuron survival. Motor neuron destruction leads to a progressive loss of muscle control, strength and function, ability to swallow and breathing, and ultimately death in the most severe forms of the disease. SMA is an early childhood disease with an incidence of approximately 1:10,000 live births and is the leading cause of infant mortality due to genetic disease. It is estimated that there are 700 SMA patients in Canada; there is an estimated 37.2 cases of newly diagnosed SMA each year in Canada.

The benefits of Zolgensma are demonstrated in multiple clinical trials that included only subjects who received Zolgensma and had either clinically diagnosed infantile-onset symptomatic SMA or genetically diagnosed presymptomatic SMA. All subjects possessed bi-allelic deletion of the SMN1 gene and either 2 or 3 copies of SMN2 gene.

Based on the natural history of infantile-onset SMA, less than 25% of patients are expected to survive past 14 months of age; in contrast, almost all subjects treated with Zolgensma remained alive and free of permanent ventilatory support up to 14 months of age. Most subjects gained the ability to sit alone, and some subjects gained the ability to stand alone and walk alone. Almost all subjects achieved an overall improvement in motor skills, which was most pronounced in presymptomatic SMA subjects. Most subjects that did not meet these milestones remained within the window of achievement in which these milestones would commonly be achieved.

Certain safety concerns have been identified for Zolgensma. One major risk of Zolgensma treatment is damage to the liver that can lead to liver failure. Another major risk is a decrease in blood platelet count that can require a platelet transfusion. These risks can be managed with appropriate medical monitoring and treatment.

Other aspects of Zolgensma safety are less certain. For example, the effects of Zolgensma on certain areas of the central nervous system (e.g., the dorsal root ganglia), on the heart, on future offspring, and when used with other drugs for the treatment of SMA have not been fully characterized. More information about these and other effects will become available through additional clinical studies and other risk monitoring activities.

Overall, the benefit-risk profile for Zolgensma is considered to be positive for the treatment of pediatric patients with 5q spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene and up to 3 copies of the SMN2 gene or infantile-onset SMA.

For more information on Health Canadas decision, please view the Summary Basis of Decision.